Calorie restriction (CR) is the only non-genetic intervention known to increase maximum lifespan and oppose a broad spectrum of age-related diseases including diabetes, sarcopenia, cardiovascular disease and cancer. A marked characteristic of animals subjected to CR is a reduction in both the amount and bioactivity of adipose tissue, an organ that has only recently been associated with the aging process. Because of the interrelationship between aging, calorie intake and adipose tissue, and because it is difficult for humans to adhere to a CR diet, there is a strong interest in identifying biomarkers of CR in adipose tissue which can be used for screening compounds that may mimic the effect of CR and oppose age-related disease. DNA microarray analysis is a powerful technique for obtaining a global profile of the expression of tens of thousands of genes in single experiment. However, microarray studies of long-term CR are expensive and time-consuming (>3 years in mice). Another concern with microarray analysis in this context is that thousands of genes are changed in response to long-term CR, and the majority of these changes in gene expression are specific to the genetic background of the mouse strain being studied. For these reasons, microarray analysis is not be feasible for large-scale screening of compounds which may mimic the effect of CR. Successful completion of the proposed research will yield a small number of genes (5-15) that are differentially expressed by short-term CR in adipose tissue of multiple strains of mice. These genes will represent robust transcriptional biomarkers of CR in adipose tissue and will likely be relevant to human health. This panel of genes can be used in future studies for rapid screening of nutrients and drugs that may mimic the effect of CR in adipose tissue. PUBLIC HEALTH RELEVANCE: Numerous studies have shown that a calorie-restricted (CR) diet extends lifespan and prevents a broad spectrum of age-related diseases but it is extremely difficult for humans to adhere to this regimen. Thus, there is a great interest in identifying nutrients and drugs that would achieve the health benefits of a CR diet. The proposed research will use a novel approach to identify the most important genes that are modulated by a CR diet, and these genetic markers can be used in the future to rapidly test dozens of compounds that may have the ability to oppose age-related diseases.